Recent developments in the genetics of alcohol-related phenotypes

This article presents the proceedings of a symposia held at the International Society for Biomedical Research on Alcoholism Congress in Mannheim, Germany, in October, 2004 and focused on recent developments in alcohol-related phenotypes from three different research groups. The first presentation focused on the possible contribution of polymorphisms of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase-2 (ALDH2) as contributors to alcohol-related organ damage. As polymorphisms of both ADH and ALDH, these genes may explain individual differences in the concentration and elimination of ethanol and acetaldehyde in the blood after heavy drinking; they may also be useful for determining their possible contribution to possible alcohol-related types of organ damage, including amnestic problems and polyneuropathy. A second presentation examined externalizing behavior phenotypes, including conduct disorder symptoms, aggression, and suicidal behavior, which are all prevalent among individuals with alcohol dependence. As part of the Collaborative Study on the Genetics of Alcoholism, a genome screen was performed in multiplex alcohol-dependent families to identify chromosomal regions related to these three types of externalizing behaviors. Both the quantitative and qualitative phenotypes were examined, and evidence of linkage was found for several chromosomal regions. An area of chromosome 2 demonstrated linkages for suicidal behavior, conduct problems, and alcohol dependence, suggesting a possible sharing of genes for different externalizing behavior phenotypes. The last presentation focused on serotonin (5-HT) as being a key neurotransmitter in antisocial alcoholism and related phenotypes. In a study of adult alcoholics, an association was found between a lower frequency of the 5-HT 113 861C allele, antisocial personality traits, and conduct disorder in alcohol dependence. Adult antisocial personality was more often found in male subjects. Based on the presented analyses, inconsistent but encouraging results were found to support the role of the 5-HT 1B G 861 C polymorphism and antisocial behavior in alcohol dependence.